REGULAR ISSUE Kesharwani et al. ___________________________________________________________________________________________________ IIOAB-India Kesharwani et al. IIOABJ; Vol. 2; Issue 7; 2011:1–10 1 www.iioab.org www.iioab.webs.com BIOINFRMATICS DESIGNING OF A MODEL FOR HUMAN AMELOGENIN FOR PREDICTING ITS ROLE IN MINERALIZATION DURING SYNTHESIS OF TOOTH ENAMEL, AN IN SILICO APPROACH Rajesh Kumar Kesharwani, Vandhana Mahajan, and Krishna Misra* Division of Applied Science and Indo-Russian Center for Biotechnology, Indian Institute of Information Technology, Deoghat Jhalwa campus, Allahabad-211012, INDIA ABSTRACT Corresponding author: Email: krishnamisra@hotmail.com; Tel: +91-9415247579, 261486; Fax: +91-532-2461376/2608469 [I] INTRODUCTION Biological materials like enamel exhibit intricate architecture and outstanding physical properties, unobtainable by traditional methods of materials synthesis. As a result, despite enormous effort no ideally biocompatible artificial tooth enamel material has so far been developed [1]. In case the mechanism of the natural process of enamel formation is understood, better materials based on the same principle can be designed which would have properties closer to the natural enamel. Enamel is composed of proteins amelogenin, ameloblastin, enamelin and tuftelin. Of these more than 90% is constituted by amelogenin. Thus, it can be considered as major protein responsible for enamel formation and has been studied under the present work. The protein has been found to exist in two major isoforms - AMELX (Amelogenin X isoform) and AMELY (Amelogenin Y isoform), encoded by AMGX and AMGY genes present on the short arms of the human X and Y chromosomes [2]. Amelogenin X was chosen for this study because it is reported that mutations in AMELX may cause Amelogenesis imperfecta, a disorder of tooth enamel development in which teeth may become usually small, discolored, pitted or grooved, and prone to rapid wear breakage [3]. Also, AMELX is the structural constituent of tooth enamel and is involved in hydroxyapatite binding and Amelogenin-Amelogenin protein binding [2]. The matrix-mediated enamel biomineralization involves secretion of the enamel specific amelogenin proteins that through self-assembly into nanosphere structures provide the framework within which the initial enamel crystallites are formed [4]. Amelogenin protein is found in the developing tooth enamel and belongs to the family of extracellular matrix (ECM) proteins. Its function is believed to be in organizing enamel crystals during tooth development. It has been found that amelogenin is primarily hydrophobic, rich in proline (25%), glutamine (14%), leucine (9%), and histidine (7%), which altogether account for more than 50% of the amino acids. The amino acid sequence can be divided into 3 domains, based on differences in composition of amino acids [1]: a). The N-terminal domain with 45-amino-acids is rich in Tyr (TRAP), The Amelogenin protein found in developing tooth enamel is believed to organize enamel crystals during tooth development by acting as a crystallization centre for mineralization. The motive of the current study was to predict the 3-D structure of human amelogenin X and mechanism of its self-aggregation using computational methods. Homology modeling followed by threading and ab-initio methods were used for structure prediction to obtain a protein model suitable to study the self-aggregation of amelogenins in-silico. The model obtained from HHPred was selected, refined, and optimized using different bioinformatics servers and softwares. On analysis, the model gave acceptable Procheck, Verify-3D, Errat and ProQ results. The predicted model could be validated by studying its intermolecular interaction to form nanospheres which is in agreement with literature reports. This predicted protein model can be used further to study the protein-mineral-protein interactions taking place in the process of amelogenesis for hypothesizing on new restorative materials. Received on: 3 rd -March-2011 Revised on: 1 st -April-2011 Accepted on: 18 th -May-2011 Published on: 1 st -Sept-2011 KEY WORDS OPEN ACCESS RESEARCH ARTICLE Tooth enamel; In silico; Homology Modeling; ramachandran plot; amelogenin ISSN: 0976-3104